This proposal from a group of investigators in the Department of Chemistry at the University of California, San Diego, is for improvements to a VAX 11/780 based computer system used to carry out research funded by NIH. The requested equipment will increase the capacity of the system an estimated 230%. The major objective of this research is to understand the functioning of biomolecules through detailed exploration of their structure and their dynamics. Major areas of biomedical research include 1) the X-ray crystallography of enzymes and substrates to derive three-dimensional structures and from this to deduce the mechanism of their biological activity; 2) the exploitation of the relationship between structure and function in rational drug design; 3) calculation by molecular mechanics of structural, dynamic, energetic, and spectral properties of peptides and depsipeptides in solution, and the use of these properties to design molecules to carry out specific biological functions; 4) the study of the dynamics by which biomolecules, particularly polypeptides and proteins, function in roles varying from ion transport in membrane pores to enzyme action; 5) the structural and dynamic properties of RNA and DNA molecules in solution using NMR techniques; and 6) the study of protein evolution using the reconstruction of past events which have led to the existing protein inventory.